Dr. Amira Taman, Ph.D.

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Research in nanotechnology is rapidly progressing

the development of new modalities for early

diagnosis and medical treatment beyond the

cellular level of individual organelles is the

goal of nanotechnology researchers.

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Nanotechnology is a general term refers to the techniques

and methods for studying, designing, and fabricating

devices at the level of atoms and molecules.

The word “nano” is derived from the Greek word

meaning ‘‘dwarf’’

In dimensional scaling nano refers to 10 -9

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Nanotechnology is very important to biology since

many biological species have molecular structures at

the nano-scale levels such as:

proteins

carbohydrates

lipids

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Nanopharmaceuticals have been targeted to every part

of the body and can even penetrate the tight epithelial

junctions of skin and endothelial interface of blood-

brain barrier (BBB) (through which 98% of drugs

cannot transverse), making high amount of drug

available to these tissues or organ.

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Lymphatic filariasis (LF) is a major health problem in

many countries due to less efficient filariasis elimination

programs.

The deep-seated location of parasites within the

complex anatomy of host lymphatic system is a barrier

resulting in less bioavailability of antifilarial agents.

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Drastic advancement in existing LF treatment protocols is

expected to be achieved by reformulating antifilarial drugs

using nanopharmaceutical technology. 7

Limitations associated with antifilarial agents for the treatment of LF.

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Advantages of using nano-medicine in Lymphatic Filariasis

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Drug Delivery Systems (DDSs)

DDSs are polymeric or lipid carriers

They can effectively transport therapeutics to their target

sites.

Advantages

1. Achieve maximum pharmacological effects

2. Minimum adverse reaction

3. Preventing the degradation/denaturation/ inactivation of therapeutic

agents. 10

Optimal size range of nanoparticles.

Efficient uptake into the lymphatic system.

High uptake in the lymph nodes.

Ability to slow release of antifilarial agents to the

parasites.

Prolong retention of drug in blood circulation to eliminate

(mf).

Low toxicity to normal, healthy tissues.11

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Liposomes are the first nanocarriers employed for the

improvement of antifilarial drugs.

Liposomes have been well studied for their accumulation in

lymph nodes or enhancing targeting to lymphatic system

via subcutaneous route.

Antibody-sensitized liposomes or immunoliposomes (as

“guided missiles”) also effectively evade mononuclear

phagocytic clearance and are considered vital for boosting

the bioavailability of microfilaricides.14

Tetracycline, doxycycline, and rifampicin are some of the

antirickettsial antibiotics found effective against Wolbachia and

can interrupt the symbiotic association between worm and

bacteria, causing death of filarial worm.

Treatment is needed for a long duration to achieve the absolute

elimination of Wolbachia, resulting in acute toxicity.

Liposomized tetracycline was found more competent than the

free form of drug, reducing the treatment plan to 12 alternate

days with better efficacy in contrast to 90/120 days oral

administration of the free drug.15

Solid lipid nanoparticles (SLNs) are attractive

pharmaceutical carriers formed of solid lipids that

remain solid at room temperature.

These nanoparticles put forward certain additional

advantages over other carriers in terms of toxicity,

biocompatibility, and controlled drug-release kinetics.

SLNs to target intracellular bacteria Wolbachi.

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Polymeric nanoparticles are colloidal particles, ranging

in size from 1 to 1000 nm.

A variety of biocompatible and biodegradable

polymeric matrices are available for their preparation.

In the recent years, polymer-based DDSs had widely

been used for the treatment of parasitic diseases and

site-specific targeting of diagnostic agents to the

lymphatic system.

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Optimal particle size range for antifilarial drug delivery

From the previous studies, the researchers suggest 20--

70 nm diameter as the most favorable size range of

nanocarriers for lymphatic targeting of antifilarials.

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Surface engineering for enhanced localization of antifilarials in the lymphatic system

Surface characteristics of nanoparticles have

fundamental importance to interact with the environment

Owing to the peculiar anatomy of lymphatic system and

interstitial resistance exerted by osmotic pressure that

prevent particles uptake, surface modifications of

polymeric nanoparticles are essential to enhance

localization of antifilarials close to lymph-resident

filaroids.19

Some ligands may prove useful for filarial treatment are

Hyaluron, L-selectin, lectin, folate, dextrin.

Mannose attached to liposome surface increases lymph node

uptake by threefold compared with control liposomes and is used

to improve the delivery of antifilarials to lymph nodes.

Also, Wolbachia, expose mannose receptors on their surface and

attract lectin-coated nanoparticles to target these bacteria.

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Avoidance of reticuloendothelial system for systemic elimination of

nanoparticles

Uptake via RES can be avoided by coating of nanoparticles

with hydrophilic polymers such as PEG and poloxamine.

The proposed mechanism for this is that these hydrophilic

polymers result in adsorption of proteins on the surface of the

nanoparticles which decrease opsonization in vivo.

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Thank you